ArticleProceedings of the National Academy of Sciences of the United States of America2016
Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 141 citations in OpenAlex.
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Phase separation across membranes and condensates in cell organization and function.Nature reviews. Molecular cell biology · 2026Review
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- Plasma membrane invaginations and their diverse cellular functions.BMC biology · 2026Review
- Multivalent adaptor networks generate nanoscale organisation within T cell signalling condensates.bioRxiv : the preprint server for biology · 2026Article
- Positive cooperativity between RAS-binding and cysteine-rich domains regulates RAF membrane binding kinetics via lateral rebinding.Nature communications · 2026Article
- Quantitative Mapping of the Lipid Nanoenvironment around Transmembrane Proteins in Living Cells.ACS nano · 2026Article
- Poly-ubiquitylated transmembrane proteins outcompete other cargo for limited space inside clathrin-coated vesicles.Cell reports · 2025Article
- A unifying model of LAT condensates in reconstitution experiments.bioRxiv : the preprint server for biology · 2025Article
- Transmembrane coupling drives the growth of liquid-like protein condensates.Biophysical journal · 2025Article
- Condensate-membrane interactions shape membranes, tune cytoskeletal assembly, and localize mRNAs.Current opinion in cell biology · 2025Review
- Enzymatic Reactions Dictated by the 2D Membrane Environment.The journal of physical chemistry letters · 2025Article
- Step-Wise Assembly of LAT Signaling Clusters Immediately After T Cell Receptor Triggering Contributes to Signal Propagation.International journal of molecular sciences · 2025Article
- Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A spatial model of autophosphorylation of CaMKII predicts that the lifetime of phospho-CaMKII after induction of synaptic plasticity is greatly prolonged by CaM-trapping.Frontiers in synaptic neuroscience · 2025Article
- Biophysical and Structural Features of αβT-Cell Receptor Mechanosensing: A Paradigmatic Shift in Understanding T-Cell Activation.Immunological reviews · 2025Review
- A spatial model of autophosphorylation of CabioRxiv : the preprint server for biology · 2024Article
- Article
- Synaptotagmin-1 undergoes phase separation to regulate its calcium-sensitive oligomerization.The Journal of cell biology · 2024Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. The generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.